Nickel‐Catalyzed Asymmetric Reductive Carbo‐Carboxylation of Alkenes with CO₂

Abstract

Reductive carboxylation of organo (pseudo)halides with CO 2 is ap owerfulm ethod to providec arboxylic acids quickly.Notably,the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO 2 fixation is ah ighly challenging but desirable approach for structurally diverse carboxylic acids.T here are only af ew reports and no examples of alkenes via transition metal catalysis.W er eport the first asymmetric reductive carbo-carboxylation of alkenes with CO 2 via nickel catalysis.Avariety of aryl (pseudo)halides,s uch as aryl bromides,a ryl triflates and inert aryl chlorides of particular note,u ndergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing aC3-quaternary stereocenter.T his transformation features mild reaction conditions,w ide substrate scope,f acile scalability,g ood to excellent chemo-, regio-and enantioselectivities.T he method highlights the formal synthesis of (À)-Esermethole, (À)-Physostigmine and (À)-Physovenine,a nd the total synthesis of (À)-Debromoflustramide B, (À)-Debromoflustramine Ba nd (+ +)-Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO 2 .

Tandem Functionalization‐Carboxylation Reactions of π‐Systems with CO2

“…Simultaneously to our group, Kong and Yu reported the nickel‐ catalyzed enantioselective intramolecular carbo‐carboxylation of methacrylanides 50 for the synthesis of oxindole 3‐acetic acids 51 bearing a defined C3‐quaternary stereogenic center. [ 20 ] In this case the PN chiral ligand I gave the best performances, and, similarly to our methodology, sterically demanding substituents on the aromatic ring or on the alkene motif were well tolerated (Figure 14). This protocol was applicable not only to activated aryl bromides, but also o ‐chloroaniline derivatives were amenable with a similar chemical output.…”

Palladium‐Catalyzed Carbamoyl‐Carbamoylation/ Carboxylation/Thioesterification of Alkene‐Tethered Carbamoyl Chlorides Using Mo(CO)6 as the Carbonyl Source

“…Additionally, selective bromination of 5 aa took place smoothly to give 9 in 85% yield (Scheme 4b). Notably, our prepared product 5 hl could be served as a key intermediate for MNKS inhibitors synthesis (Scheme 4c) [15,16] . Moreover, the product 5 ql can be easily transformed to give the bioactive molecules, such as Esermethole, Physostigmine and Physovenine (Scheme 4d) [15,17,18] …”

Nickel‐Catalyzed Asymmetric Reductive Carbo‐Carboxylation of Alkenes with CO2

“…Thec hemical structure and absolute configuration of (R)-2g (CCDC 2030840) and (R)-2n (CCDC 2030841) were further assigned by single-crystal X-ray diffraction analysis. [22] The stereochemistry of other compounds was assigned by analogy.…”